Impact of research on cyanobacterial toxins on governmental and regulatory authority guidelines on water safety.
Submitting InstitutionUniversity of Dundee
Unit of AssessmentBiological Sciences
Summary Impact TypeEnvironmental
Research Subject Area(s)
Biological Sciences: Biochemistry and Cell Biology, Ecology, Plant Biology
Summary of the impact
Cyanobacteria (blue-green algae) occur globally and produce a wide range
of potent toxins (cyanotoxins) that can be among the most hazardous
natural products in aquatic environments. Research by the University of
Dundee uncovered the biochemical mechanism of action of the microcystin
family of cyanotoxins, which resulted in the development of new cyanotoxin
detection and analytical methods, and demonstrated the health risks of
cyanotoxins. This body of research has had a direct impact on several
governmental and regulatory authority guidelines on water safety,
resulting in the implementation of procedures to reduce the risks
presented by cyanotoxins to water-users.
Surveys in different parts of the world have found that 45-90% of blooms
of blue-green algae produce toxins. These include hepato-, neuro-, and
cytotoxins, carcinogens and tumour promoters. Since the early 1980s, the
University of Dundee has worked to elucidate the health hazards of
cyanobacterial toxins and develop new methods for their analysis and
detection (including Refs 1-6). In 1990, Prof Carol MacKintosh
(Programme Leader at the MRC Protein Phosphorylation Unit) together with Prof
Geoff Codd FRSE (Professor of Microbiology at College of Life
Sciences from 1972-2010) discovered that microcystin-LR, a potent
hepatotoxin produced by cyanobacteria, inhibited protein phosphatases 1
(PP1) and 2A (PP2A) (FEBS Lett, 264,187-192). This has become one
of the most highly cited papers in this field (739 citations at November
Documented incidents on human and animal health in the late
eighties/early nineties following exposure to cyanobacterial blooms caused
increasing public concern. Suitable analytical techniques for drinking
water analysis were not available and there was insufficient toxicological
data to set health-based guidelines or standards for drinking water in the
UK. In 1994, Prof Codd developed a new and rapid methodology based on
high-performance liquid chromatography to analyse cyanobacterial
microcystins in raw and treated waters (1). At the same time, Prof
MacKintosh and colleagues dissected the biochemical mechanism of
microcystin binding to phosphatases (2,3). Prof MacKintosh then
collaborated with Thames Water Utilities to develop and use new methods
for detection of cyanobacterial toxins based on protein phosphatase
Before 1998, cyanobacteria were known to have caused deaths in livestock,
domestic animals and wildlife; however evidence concerning the risk to
humans of cyanotoxin exposure via drinking water, accidental ingestion or
recreational contact, was mostly circumstantial (4). Dundee researchers
helped to highlight the public health dangers of cyanotoxins. In 1997,
MacKintosh and colleagues demonstrated that there were significant levels
of microcystin and cyanobacteria in Irish lakes (5). A key report by Codd
in the Lancet in 1998 revealed that the death of 60 patients in a
haemodialysis unit in Caruaru, north-east Brazil, could be attributed to
exposure to highly toxic microcystins in the water supply from a lake with
massive growth of cyanobacteria (6). This report had far reaching public
health implications and resulted in recognition that haemodialysis
represented a high-risk exposure route for poisoning by cyanobacterial
toxins and suggested that water used for dialysis required special
processing. Moreover, the Dundee discovery that microcystin binds
covalently to protein phosphatases (3) explained why hepatic levels of
free toxin were lower than expected in post-mortem analyses in the
Brazilian case, and in suspected cases of microcystin poisoning in
animals. The Dundee findings that microcystin shares the same binding site
as the tumour promoter okadaic acid highlighted that management strategies
should be set to prevent chronic exposure to low doses of microcystin.
Continuing research from Dundee researchers has helped determine
procedures for the risk management of cyanobacterial toxins, including
derivation of tolerable daily intakes and guideline values for the
cyanobacterial toxins in drinking water, and for toxigenic cyanobacteria
in bathing waters.
References to the research
1. Lawton, L.A., Edwards, C. and Codd, G.A. (1994) Extraction and
high-performance liquid chromatographic method for the determination of
microcystins in raw and treated waters. Analyst 119, 1525-1530.
(doi:10.1039/AN9941901525) (Citations 348, Scopus Nov 2013).
2. Moorhead G., MacKintosh R.W., Morrice N., Gallagher T. & MacKintosh
C. (1994) Purification of type 1 protein (serine/threonine)
phosphatases by microcystin-Sepharose affinity chromatography. FEBS Lett.
356, 46-50. (doi:10.1016/0014-5793(94)01232-6) (Citations 123,
Scopus Nov 2013).
3. MacKintosh, R.W., Dalby, K.N., Campbell, D.G., Cohen, P.T.W., Cohen,
P., MacKintosh,C. (1995) The cyanobacterial toxin microcystin
binds covalently to cysteine-273 on protein phosphatase 1. FEBS Lett. 371,
236-240. (doi:10.1016/0014-5793(95)00888-G) (Citations 153, Scopus Nov
4. Codd, G.A (1995) Cyanobacterial toxins: occurrence, properties
and biological significance. Water Science and Technology. 32,
149-156. (doi:10.1016/0273-1223(95)00692-3) (Citations 229, Scopus Nov
5. Sherlock, I.R., James, K.J., Caudwell, F.B., and MacKintosh, C.
(1997) First identification of microcystins in Irish lakes aided by a new
derivatisation procedure for electrospray mass spectrometric analysis. Nat
Toxins 5, 247-254.
(Citations 11, Scopus Nov 2013).
6. Pouria, S., de Andrade, A., Barbosa, J., Cavalcanti, R.L., Barreto,
V.T.S., Ward, C.J., Preiser, W., Poon, G.K., Neild, G.H. and Codd,
G.A. (1998) Fatal microcystin intoxication in haemodialysis unit in
Caruaru, Brazil. The Lancet 352, 21-26.
(doi:10.1016/S0140-6736(97)12285-1) (Citations 347, Scopus Nov 2013).
Details of the impact
(a) The World Health Organisation (expert opinion that shaped
international Guidelines for Drinking Water Quality)
(b) The UK Department of the Environment and Thames Water Utilities Ltd
(development and use of phosphatase inhibition assays to monitor
cyanotoxin levels in reservoirs and drinking water)
(c) Scottish, US, Canadian, New Zealand, and Australian environmental
authorities (expert opinion that shaped guidelines relating to cyanotoxins
in recreational and drinking water)
(d) The general public at risk from cyanotoxin exposure in drinking
water, dialysis fluid or in lakes and rivers.
Research by the University of Dundee has had a major impact on the
recognition, toxicity-assessment and risk-management of cyanobacterial
blooms and cyanotoxins in waterbodies worldwide. This research provided
primary guidance in the formulation and adoption of safety plans by
several governmental and regulatory authorities for health protection
against cyanotoxins in human drinking water supplies, aquaculture and
In 1999, Professor Codd played a major role in preparing one of the most
comprehensive and highly cited texts in the cyanobacteria field "Toxic
Cyanobacteria in Water: A Guide to their Public Health Consequences,
Monitoring and Management" which was published by the World Health
Organization. Professor Codd authored chapters 5, 7, 10, and section 8.5.8
as well as participating in the editorial advisory group. The guide
detailed the information needed for protecting drinking-water sources and
recreational water bodies from the health hazards caused by cyanobacteria
and their toxins. This text was key in the derivation of the World Health
Organisation (WHO) guidelines for Drinking Water Quality (1,2). These
guidelines, published in 2008 and updated in 2011 (and frequently citing
primary research from Professor Codd) are one of the most significant
policy documents for the management of water resources (1,2) and represent
the current position of "UN-Water", the body that coordinates programmes
concerned with water issues amongst the 24 UN agencies.
In addition, Prof MacKintosh was a discussant at the Water Toxins Panel
of the Department of the Environment Standing Committee of Analysts
(Organic Impurities Working Group) from 1992 to 1996 and was a consultant
to Thames Water Utilities Ltd. (1994-1995), advising on use of protein
phosphatase assays to detect microcystin in water samples. This resulted
in the use of new analytical methods to monitor water safety during a
period of microcystic blooming on reservoirs in the Thames area which are
still in use today.
Other current governmental and regulatory authority guidelines have been
heavily influenced by cyanotoxin research at the University of Dundee.
1) Guidance to Public Health and Environmental Health Authorities in
Scotland (2012), on risks of cyanobacteria in inland and inshore waters
(3). Professor Codd was part of the Working group that prepared this
document and the guidance commissioned by the Scottish Government takes
account of current WHO guidelines (2).
2) The Guidelines for Canadian Recreational Water Quality (2012)
(4) is used by provincial and local authorities in Canada and provides
advice on the health risks of recreational waters.
3) Guidelines For Managing Risks in Recreational Water (2008) (5)
is a document produced by the Australian Government for state and
territory governments to develop legislation and standards to manage the
quality of coastal, estuarine and fresh waters used for recreation.
4) The US Council on Environmental Quality commissioned an Interagency
Working Group on Harmful Algal Blooms, Hypoxia, and Human Health to
produce a 2008 report assessing the problem of harmful algal blooms in
inland waters of the US (6).
5) The US Geological Survey published guidelines in 2008 for the design
and sampling for cyanobacterial toxin in lakes and reservoirs (7).
6) The US Environmental Protection Agency published a fact sheet in 2012
(8) providing basic information on human health effects, analytical
screening tools, and the effectiveness of various treatment processes to
remove or inactivate the three most important cyanotoxins that occur in US
7) The New Zealand Ministry for the Environment and Ministry of Health
published guidelines in 2009 to promote a unified approach to managing
cyanobacterial risk in water used for recreational purposes (9).
The development of microcystin-Sepharose to purify and characterize
protein phosphatases and their diverse regulatory subunits by the
University of Dundee was adopted by Millipore and this reagent is marketed
Sources to corroborate the impact
- WHO (2008) Guidelines for drinking-water quality, Third edition
incorporating the first and second addenda, Volume 1: Recommendations,
World Health Organization, Geneva. ISBN: 9789241547611 http://www.who.int/water_sanitation_health/dwq/GDWPRecomdrev1and2.pdf
- WHO (2011) Guidelines for drinking-water quality, Fourth edition
Geneva, Switzerland, World Health Organization. Xiii 541p. ISBN:
- Scottish Government (2012) Cyanobacteria (Blue-Green Algae) in Inland
and Inshore Waters: Assessment and Minimisation of Risks to Public
Health. Scottish Government Health & Social Care Directorates. ISBN:
- Health Canada (2012). Guidelines for Canadian Recreational Water
Quality, Third Edition. Water, Air and Climate Change Bureau, Healthy
Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario.
ISBN: 9781100208923 http://www.hc-sc.gc.ca/ewh-
- Australian Government (2008) Guidelines For Managing Risks in
Recreational Water. National Health and Medical Research Council. ISBN
Online: 1864962720 http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/eh38.pdf
- Lopez, C.B., Jewett, E.B., Dortch, Q., Walton, B.T., Hudnell, H.K.
(2008). Scientific Assessment of Freshwater harmful Algal Blooms.
Interagency Working Group in Harmful Algal Blooms, Hypoxia, and Human
Health of the Joint Subcommittee on Ocean Science and Technology.
Washington, DC. http://www.whoi.edu/fileserver.do?id=41023&pt=10&p=19132
- Graham, J.L., Loftin, K.A., Ziegler, A.C., and Meyer, M.T. (2008)
Guidelines for design and sampling for cyanobacterial toxin and
taste-and-odor studies in lakes and reservoirs: U.S. Geological Survey
Scientific Investigations Report 2008-5038, 39 p. http://www.jlakes.org/web/SIR2008-5038.pdf
- United States Environmental Protection Agency Office of Water 4304T
(2012) Cyanobacteria and Cyanotoxins: Information for Drinking Water
Systems, EPA-810F11001. http://water.epa.gov/scitech/swguidance/standards/criteria/nutrients/upload/cyanobacteria_facts
- Ministry for the Environment and Ministry of Health (2009) New
Zealand Guidelines for Cyanobacteria in Recreational Fresh Waters —
Interim Guidelines. Prepared for the Ministry for the Environment
and the Ministry of Health by SA Wood, DP Hamilton, WJ Paul, KA Safi and
WM Williamson. Wellington: Ministry for the Environment. ISBN: